An Influenza Viral Swarm

Amesh A. Adalja, MD, FACP, FACEP, FIDSA, January 8, 2016

In many viral infectious diseases, it is often believed that a single strain of a virus is responsible for the disease and that a diagnostic test may confirm that a person is infected with a specific strain of a specific virus. However, it is becoming increasingly clear that this notion is too simplistic. Many viruses have very high mutation rates, and, as a result, there may be many variants within a single infected individual. What may seem, according to ordinary diagnostic tests, to be a mono-infection may in fact be a viral swarm.

New research from Poon and colleagues, published in Nature Genetics, shows how this phenomenon is at work in influenza.

Household Sampling During 2009 Pandemic

In this study, 84 individuals (67 index patients and 17 household members) in Hong Kong were sampled during July and August of 2009. At the time, both the 2009 H1N1 pandemic influenza virus and the H3N2 influenza virus were co-circulating. Using deep sequencing, 3 sublineages of H3N2 and 3 clades of pandemic H1N1 were determined to be present in subjects.

By comparing single-nucleotide variants, transmission networks were established, and it was estimated that 66% of H3N2 patients and 40% of H1N1 patients had mixed-lineage infections that arose both from new mutations and transmission events. The investigation also addressed the number of viral particles needed for infection by using the frequency of certain genetic markers in household-spread viruses. Just 100-200 virus particles were found to be the effective viral population size for transmission.

Swarm of Viruses

The implications of this important paper are far-reaching because they establish that, despite the convenience of thinking of influenza infections in a person as a monolithic event, there is truly a swarm of related but distinct viruses lying beneath what is detected conventionally.

These cryptic viruses may not be fully covered by vaccines, may harbor disparate antiviral resistance patterns, or could act as harbingers that later emerge to become major contributors to future influenza seasons.

Future research efforts to understand the epidemiologic trajectory of these minor variants and their clinical relevance will be an important aspect of influenza preparedness.